Journal Article Review Epublish
PubMed: 40269912 DOI: 10.1186/s13024-025-00837-w
Research models to study lewy body dementia.
Mol Neurodegener 20(1):46
Authors: Suelen Lucio Boschen, Aarushi A Mukerjee, Ayman H Faroqi, Ben E Rabichow, John Fryer
Affiliations
- Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
- Department of Neurosurgery, Mayo Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
- Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA.
- Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
- Translational Genomics Research Institute, 445 N 5th St, Phoenix, AZ, 850054, USA.
Abstract
Lewy body dementia (LBD) encompasses neurodegenerative dementias characterized by cognitive fluctuations, visual hallucinations, and parkinsonism. Clinical differentiation of LBD from Alzheimer's disease (AD) remains complex due to symptom overlap, yet approximately 25% of dementia cases are diagnosed as LBD postmortem, primarily identified by the presence of α-synuclein aggregates, tau tangles, and amyloid plaques. These pathological features position LBD as a comorbid condition of both Parkinson's disease (PD) and AD, with over 50% of LBD cases exhibiting co-pathologies. LBD's mixed pathology complicates the development of comprehensive models that reflect the full spectrum of LBD's etiological, clinical, and pathological features. While existing animal and cellular models have facilitated significant discoveries in PD and AD research, they lack specificity in capturing LBD's unique pathogenic mechanisms, limiting the exploration of therapeutic avenues for LBD specifically. This review assesses widely used PD and AD models in terms of their relevance to LBD, particularly focusing on their ability to replicate human disease pathology and assess treatment efficacy. Furthermore, we discuss potential modifications to these models to advance the understanding of LBD mechanisms and propose innovative research directions aimed at developing models with enhanced etiological, face, predictive, and construct validity.
MeSH
Dementia, Lewy Bodies, Pathology, Lewy Body Disease, Research, Therapeutics